Increased colon N-palmitoylethanolamine levels via enzyme inhibition leads to reduction of colitis

In an elegant murine model Muccioli et al from Belgium explored the fact that N-Palmitoylethanolamine or palmitoylethanolamide (PEA) can be metabolised by the less-studied enzyme N-acylethanolamine-hydrolyzing acid amidase (NAAA).

An enzyme inhibitor of this enzyme, responsible for PEA hydrolysis, could be of great value in colon inflammation and would be a potential therapeutic target for inflammatory bowel diseases (IBDs).

In two murine models of IBD, the effects of NAAA inhibition and PEA were studied on macroscopic signs of colon inflammation, macrophage/neutrophil infiltration, and on the expression of proinflammatory mediators in the colon, as well as on the colitis-related systemic inflammation.

NAAA inhibition increases PEA levels in the colon and reduces colon inflammation and systemic inflammation, similarly to the administration of PEA.


This is the first report of an anti-inflammatory effect of a systemically administered NAAA inhibitor. Because NAAA is the enzyme responsible for the control of PEA levels in the colon, we put forth this enzyme as a potential therapeutic target in chronic inflammation in general and IBD in particular.

However, inhibiting such enzymes seem not to bring anything new, apart from the perspective of patents, and mostly inhibiting enzymes have complicated side effects. As PEA itself has comparable biological effects it is recommended to stick to PEA. Moreover, the development of such inhibitors will take many many years before it can be tested in patients.

Alhouayek M, Bottemanne P, Subramanian KV, Lambert DM, Makriyannis A, Cani PD, Muccioli GG. N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis. FASEB J. 2014 Nov 10. pii: fj.14-255208.

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